硼中子俘获治疗的微剂量学研究现状

微剂量学研究在临床硼中子俘获治疗(BNCT)的计划设计和疗效评价中起着重要作用。设计一套既能准确描述10B化合物及其反应产生的次级粒子在细胞、亚细胞水平的剂量不均匀分布,又适合于临床上使用的微剂量估算模式,一直是此领域的研究重点。为此,着重介绍了BNCT的微剂量估算方法及其最近发现显著影响其精确度的因素。     

快中子放疗同时硼中子俘获治疗

中子用于肿瘤的临床治疗主要有两种形式:快中子放疗(FNRT)和硼中子俘获治疗(BNCT)。中子优越的放射生物学特性可以更有效地杀伤某些肿瘤,但是这两种治疗手段都存在着某些尚待解决的问题。将两种治疗结合起来可能产生临床上更理想的治疗增益,因此有必要对FNRT同时BNCT做进一步的实验室及临床方面的研究。本文将从以下四个方面讨论中子放疗的情况;①快中子放疗。②硼中子俘获治疗。③BNCT与FNRT同时进行可增强快中子放疗的效果。④今后研究的方向。这里重点探讨BNCT增加FNRT有效的物理及生物剂量问题。     

肿瘤硼中子俘获治疗的理论基础与近期研究进展

硼中子俘获治疗(BNCT)是一种新型肿瘤精准治疗方法 ,通过肿瘤细胞内的10B俘获热中子发生核裂变反应产生a粒子和反冲7Li核选择性地杀死肿瘤细胞.将足量的10B选择性递送到肿瘤细胞内部是BNCT成功的关键.本文简要介绍了BNCT治疗肿瘤的理论基础,综述了BNCT所用的中子源和硼递送剂的近期研究进展,简述了BNCT临床...     

硼中子俘获治疗的辐射场特点与剂量估算

BNCT(硼中子俘获治疗)基于这样一种思想:10B的载体化合物会优先选择癌细胞作为靶而后与热中子反应,进而产生高能、短射程裂变产物α粒子和Li粒子。它是一种双重的靶向治疗方法。BNCT的治疗效果依赖于两个主要因素:源于10B(n,α)7Li核反应的高LET(传能线密度)粒子的生物效应和在靶细胞及其特异区域内的硼沉积。本文总结和探讨了BNCT的发展概况、辐射场的特点以及吸收剂量的计算方法。     

硼中子俘获治疗的辐射场特点与剂量估算

BNCT（硼中子俘获治疗）基于这样一种思想：^10B的载体化合物会优先选择癌细胞作为靶而后与热中子反应，进而产生高能、短射程裂变产物α粒子和Li粒子。它是一种双重的靶向治疗方法。BNCT的治疗效果依赖于两个主要因素：源于^10B（n,α）^7Li核反应的高LET（传能线密度）粒子的生物效应和在靶细胞及其特异区域内的硼沉积。本总结和探讨了BNCT的发展概况、辐射场的特点以及吸收剂量的计算方法。     

硼中子俘获治疗技术的研究现状

对硼中子俘获治疗技术的原理、硼中子俘获治疗系统需要研究的相关内容及研究现状作了主要介绍；对加速器或反应堆产生超热中子束的方法及与硼中子俘获治疗相关的硼化合物作了较详细的讨论。     

硼中子俘获治疗技术的研究现状

对硼中子俘获治疗技术的原理、硼中子俘获治疗系统需要研究的相关内容及研究现状作了主要介绍;对加速器或反应堆产生超热中子束的方法及与硼中子俘获治疗相关的硼化合物作了较详细的讨论。     

中子剂量测量及估算方法

随着科技的发展,中子在许多行业得到越来越广泛的应用,在医疗上应用最广泛的是硼中子俘获治疗.但在使用中子辐射的过程中,操作人员可能会受到中子辐射,因此中子剂量的测量和估算问题也就变得重要起来.目前,国内关于中子剂量的研究在有些方面还不是很深人,因此对中子剂量的测量和估算方法进行了归纳和阐述.     

硼中子俘获治疗头颈部肿瘤临床试验进展

硼中子俘获治疗（boron neutron capture therapy,BNCT）是结合靶向治疗和重离子治疗的先进二元放疗技术。其原理是利用含有¹⁰B同位素的硼药在肿瘤细胞中靶向聚集,随后中子束流外部照射肿瘤部位,发生¹⁰B（n,α）⁷Li核反应,释放出杀伤范围为一个细胞大小（5~9 μm）的高传能线密度α粒子和⁷Li粒子杀死肿瘤细胞。BNCT具有精准的肿瘤靶向性,对正常组织损伤小,分割次数（1~3次）少于传统放疗（30次）等优点。BNCT使用的中子由反应堆或加速器产生,临床使用的硼药包括BPA和BSH两种。本文介绍国内外开展的头颈部肿瘤BNCT临床试验及取得的重要进展。BNCT对于头颈部肿瘤治疗具有良好疗效。随着加速器中子源的推广应用和新型硼药的研发,BNCT将会在临床放射治疗领域发挥更大的作用。     

用于硼中子俘获治疗的超热中子束理论设计

目的 设计用于硼中子俘获治疗(BNCT)的超热中子束理论方案。方法 基于清华大学试验核反应堆,以其1号孔道为材料布放孔道,设计了由慢化材料、热中子吸收材料、γ屏蔽材料组成,但材料布放位置具有差异的5种理论方案;利用蒙特卡罗(MC)模拟方法,分别计算5种方案束出口处的中子注量率、剂量率及γ剂量率值,通过与BNCT技术指标对比,从5种方案中选择一种合适的方案。结果 得到了一个符合BNCT各项技术指标的超热中子束理论方案,其慢化材料厚度为53.5 cm、热中子吸收材料厚度为2 mm、γ屏蔽材料厚度为9 cm。结论 本研究给出的超热中子束理论方案为基于反应堆实现BNCT提供一定的理论参考。     

The TL analysis methods used to determine absorbed gamma doses in vivo for the BNCT patients treated at FiR 1.

The gamma dose determination using thermoluminescent (TL) dosimeters in mixed neutron-gamma fields, such as in boron neutron capture therapy (BNCT), is difficult due to the thermal neutron sensitivity of the detectors; especially when equipment capable of glow curve analysis is not available. The two TL analysis methods used previously in Finnish BNCT to correct the measured TL signal to obtain absorbed gamma dose in vivo were studied and compared, and an enhanced method was introduced. The three TL methods were found surprisingly consistent despite, e.g. the rough estimate made in the first method.     

In-phantom imaging of all dose components in boron neutron capture therapy by means of gel dosimeters.

The experimental method for in-phantom imaging and profiling the absorbed dose in neutron capture therapy has been improved. The method separates the contributions of the various secondary radiation components and is based on suitably designed gel dosimeters in the form of layers. The discrimination of the dose components is achieved by means of pixel-to-pixel manipulations of images obtained with gel dosimeters having different isotopic composition. Large dose images are obtainable with this method, because the layer geometry of dosimeters avoids sensible variation of neutron transport due to the isotopic composition of gel. Operation modalities aimed at attaining more reliable results have been studied. Some results, together with the results of punctual measurements performed with conventional dosimeters and with MC calculations, are here reported.     

Long-survivors of glioblatoma treated with boron neutron capture therapy (BNCT)

The purpose of this study was to compare the radiation dose between long-survivors and non-long-survivors in patients with glioblatoma (GBM) treated with boron neutron capture therapy (BNCT). Among 23 GBM patients treated with BNCT, there were five patients who survived more than three years after diagnosis. The physical and weighted dose of the minimum gross tumor volume (GTV) of long-survivors was much higher than that of non-long survivors with significant statistical differences.     

Accumulation of boron compounds to tumor with polyethylene-glycol binding liposome by using neutron capture autoradiography.

The cytotoxic effect of boron neutron capture therapy (BNCT) is due to a nuclear reaction between 10B and thermal neutrons. It is necessary to accumulate the 10B atoms to the tumor cells selectively for effective BNCT. In order to achieve an accurate measurement of 10B concentrations in the biological samples, we employed a technique of neutron capture autoradiography (NCAR) of the sliced whole-body samples of tumor bearing mice using CR-39 plastic track detectors. The CR-39 detectors attached with samples were exposed to thermal neutrons in the thermal column of the TRIGA II reactor at the Institute for Atomic Energy, Rikkyo University and thermal neutron facility of Paul Scherer Institute(PSI). We obtained NCAR images for mice injected intravenously by 10B-PEG liposome, 10B-transferrin-PEG liposome, or 10B-bare liposome. The 10B concentrations in the tumor tissue of mice were estimated by means of alpha-track density measurements. In this study, we can increase the accumulation of 10B atoms in the tumor tissues by binding polyethylene-glycol chains to the surface of liposome, which increase the retention in the blood flow and escape the phagocytosis by reticulo-endothelial systems. Therefore, we will be able to apply NCAR technique for selection of effective 10B carrier in BNCT for cancer.     

BNCT dose distribution in liver with epithermal D-D and D-T fusion-based neutron beams.

Recently, a new application of boron neutron capture therapy (BNCT) treatment has been introduced. Results have indicated that liver tumors can be treated by BNCT after removal of the liver from the body. At Lawrence Berkeley National Laboratory, compact neutron generators based on (2)H(d,n)(3)He (D-D) or (3)H(t,n)(4)He (D-T) fusion reactions are being developed. Preliminary simulations of the applicability of 2.45 MeV D-D fusion and 14.1 MeV D-T fusion neutrons for in vivo liver tumor BNCT, without removing the liver from the body, have been carried out. MCNP simulations were performed in order to find a moderator configuration for creating a neutron beam of optimal neutron energy and to create a source model for dose calculations with the simulation environment for radiotherapy applications (SERA) treatment planning program. SERA dose calculations were performed in a patient model based on CT scans of the body. The BNCT dose distribution in liver and surrounding healthy organs was calculated with rectangular beam aperture sizes of 20 cm x 20 cm and 25 cm x 25 cm. Collimator thicknesses of 10 and 15 cm were used. The beam strength to obtain a practical treatment time was studied. In this paper, the beam shaping assemblies for D-D and D-T neutron generators and dose calculation results are presented.     

Effects of boron neutron capture therapy on human oral squamous cell carcinoma in a nude mouse model

PURPOSE: The effect of boronophenylalanine (BPA)-mediated boron neutron capture therapy (BNCT) on human oral squamous cell carcinoma (SCC) xenografts in nude mice was examined. MATERIALS AND METHODS: Tumor-bearing mice were given BPA at a dose of 250 mg/kg body weight. The tumor (10)B concentration 2 h after an injection of BPA was higher than those 1 or 3 h after the injection. Neutron irradiation was performed beginning 1, 2 or 3 h after an injection of BPA and the effects on body weight of the animals, tumor growth, survival of tumor-bearing animals, and histology of tumor and normal tissue were examined. Fragmented nuclear DNA, 5-bromo-2'-deoxyuridine (BrdU), and von Willebrand Factor (vWF) were detected by immunohistochemical staining. RESULTS: Tumor volumes of untreated control animals increased continuously, whereas those of BNCT-treated animals were markedly decreased. Animals given neutron irradiation 2 h after the injection of BPA survived for a longer period as compared with those given neutron irradiation 1 or 3 h after the injection. BNCT reduced the incorporation of BrdU into tumor cells, and induced the enlargement and vacuolation of tumor cells. Disintegration of blood vessels and dense inflammatory cell infiltration were also observed in the stroma of the tumor, but not surrounding normal tissues. CONCLUSION: These results indicate that BPA-mediated BNCT can exert a curative effect on human oral SCC xenografts in nude mice, if an optimal 10B concentration in tumors is achieved and that the disintegration of blood vessels in tumor stroma may contribute to tumor remission by BNCT.     

Radiobiology of BNCT mediated by GB-10 and GB-10+BPA in experimental oral cancer.

We previously reported biodistribution and pharmacokinetic data for GB-10 (Na(2)(10)B(10)H(10)) and the combined administration of GB-10 and boronophenylalanine (BPA) as boron delivery agents for boron neutron capture therapy (BNCT) in the hamster cheek pouch oral cancer model. The aim of the present study was to assess, for the first time, the response of hamster cheek pouch tumors, precancerous tissue and normal tissue to BNCT mediated by GB-10 and BNCT mediated by GB-10 and BPA administered jointly using the thermalized epithermal beam of the RA-6 Reactor at the Bariloche Atomic Center. GB-10 exerted 75.5% tumor control (partial+complete remission) with no damage to precancerous tissue around tumor or to normal tissue. Thus, GB-10 proved to be a therapeutically efficient boron agent in this model despite the fact that it is not taken up selectively by oral tumor tissue. GB-10 exerted a selective effect on tumor blood vessels leading to significant tumor control with a sparing effect on normal tissue. BNCT mediated by the combined administration of GB-10 and BPA resulted in a reduction in the dose to normal tissue and would thus allow for significant escalation of dose to tumor without exceeding normal tissue tolerance.     

Discrimination of various contributions to the absorbed dose in BNCT: Fricke-gel imaging and intercomparison with other experimental results.

A method is described for the 3D measurements of absorbed dose in a ferrous sulphate gel phantom, exposed in the thermal column of a nuclear reactor. The method, studied for Boron Neutron Capture Therapy (BNCT) purposes, allows absorbed dose imaging and profiling, with the separation of different contributions coming from different secondary radiations, generated from thermal neutrons. In fact, the biological effectiveness of the different radiations is different. Tests with conventional dosimeters were performed too.